The ORL-1 (opioid receptor-like 1) receptor (see non-patent document 1, non-patent document 2) is a receptor found in 1994 as the fourth opioid receptor following δ, κ and μ receptors, and has about 60% homology of amino acid sequence with other opioid receptors. However, it is clearly different from other opioid receptors in that it is not bound with naloxone, which is a nonselective opioid receptor antagonist (see non-patent document 2). While ORL-1 receptor is also expressed in peripheral organs such as bowel, spleen and the like, it is widely distributed mainly in the central nervous system, and highly densely expressed particularly in the cerebral cortex, hippocampus, hypothalamus, amygdala and spinal cord (see non-patent document 3, non-patent document 4).
In 1995, endogenous ligands for ORL-1 receptors were sequentially identified by research groups in France and Switzerland, and named as nociceptin (see non-patent document 5) and orphanin FQ (see non-patent document 6). Nociceptin is reported to be a peptide consisting of 17 amino acids, which plays an important role in the central nervous functions such as learning, memory, anxiety and stress (see non-patent document 7).
To be specific, it has been reported that injection of a trace amount of nociceptin into hippocampus of rat induces a learning disorder in a water maze learning test (see non-patent document 8), and that nociceptin receptor-knockout mouse quickly acquires learning in a water maze learning test as compared to normal mouse (wild-type) and that the knockout mouse shows enhanced long term potentiation (LTP) in hippocampus as compared to normal mouse (see non-patent document 9). Hence, nociceptin is considered to suppressively act on the memory-learning function. In addition, it has been reported that administration of nociceptin to rat brain ventricle provides an antianxiety activity almost equivalent to that of diazepam in behavioral pharmacological tests such as conflict test, light/dark box test, elevated plus maze test and the like (see non-patent document 10). Furthermore, it has been reported that nociceptin-knockout mouse shows hypersensitivity to stress and impaired adaptability to stress as compared to normal mouse (see non-patent document 11). In other words, nociceptin is considered to have a physiological action that functions defensively to anxiety and stress, and an ORL-1 receptor agonist is considered to potentially show an antianxiety action based on an action mechanism completely different from that of benzodiazepine compounds.
From the foregoing, a compound having an ORL-1 receptor agonist activity is suggested to be useful for the treatment of mental disorder, neuropathy and physiological disorder, particularly, improvement of anxiety and stress disorder, melancholia, traumatic injury, loss of memory due to Alzheimer's disease or other dementia, symptom of epilepsy and convulsion, acute and/or chronic pain symptoms, relief of drug withdrawal symptoms including abstinence symptoms caused by cessation of abused drugs, alcohol abuse, control of water balance, Na+ excretion, arterial blood pressure disorder, eating disorder such as obesity and anorexia, and circadian rhythm sleep disorder (see patent documents 1 to 9).                non-patent document 1: FEBS Lett. 347:284-288, 1994        non-patent document 2: FEBS Lett. 341:33-38, 1994        non-patent document 3: Eur. J. Pharmacol. 340:1-15, 1997        non-patent document 4: Pharmacol. Rev. 53:381-415, 2001        non-patent document 5: Nature 377:532-535, 1995        non-patent document 6: Science 270:792-794, 1995        non-patent document 7: Br. J. Pharmacol. 129, 1261-1283, 2000        non-patent document 8: Eur. J. Neurosci. 9, 194-197, 1997        non-patent document 9: Nature 394, 577-581, 1998-14858, 1997        non-patent document 10: Proc. Natl. Acad. Sci. USA 94, 14854-10449, 1999        non-patent document 11: Proc. Natl. Acad. Sci. USA 96, 10444        patent document 1: JP-A-2000-26466        patent document 2: JP-A-11-228575        patent document 3: JP-A-10-212290        patent document 4: WO99/36421        patent document 5: WO98/54168        patent document 6: WO01/39775        patent document 7: WO00/06545        patent document 8: WO03/082333        patent document 9: WO05/028466        